A new study discovered that low vitamin D levels were strongly associated with decreased survival in patients with follicular lymphoma.
Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL), accounting for about 20% of all NHLs. NHL occurs when lymphocytes, a type of white blood cell involved in the immune system, grow and multiply uncontrollably.
The term “follicular” refers to the circular pattern in which the cells grow. FL tends to have a slow progression and responds well to treatment, but is hard to cure. Therefore, researchers and oncologists are interested in discovering modifiable prognostic and predictive factors.
A previous study found that vitamin D deficiency was an independent risk factor for the outcome of treatment in NHL patients. However, they used 8 ng/ml as the cut-off for the analysis. This study also focused on the relationship between vitamin D levels and diffuse large B-cell lymphoma, a different type of NHL than FL.
In order to provide more insight into the relationship between vitamin D status and FL, researchers recently looked at data from two independent cohorts: the Southwest Oncology Group cohort (SWOG) and the Lymphoma Study Association cohort (LYSA).
SWOG enrolled 777 previously untreated American patients with FL into three clinical trials involving CHOP, a common chemotherapy regimen used in the treatment of NHL. A total of 183 patients had available blood samples for 25(OH)D measurement, thus, only their data was used for analyses in the current study.
The LYSA (Lymphoma Study Association) cohort included 1217 previously untreated patients with FL primarily from France, Belgium and Australia. The patients were randomly divided to receive one of three chemotherapy regimens. After treatment, they were assigned to either the maintenance therapy or observation group. The purpose of the trial was to evaluate the potential benefits of maintenance therapy. Of these 1202 patients, 240 patients had blood samples for 25(OH)D measurement, and therefore, only their data was used in the present study.
Both studies observed evidence of progression of FL by clinical examinations and computed tomography scans (CT scans) throughout the studies.
The patients in the SWAG and LYSA cohort had median vitamin D levels of 31.0 ng/ml and 17.0 ng/ml, respectively. It’s important to note that there were no significant differences in the prevalence of low vitamin D levels between the different treatment regimens in both studies.
The researchers from the current study wanted to determine if there was an association between vitamin D levels and survival in patients with FL. To measure survival, they looked at progression free survival (PFS) and overall survival rates (OS). PFS refers to the length of time during and after the treatment of a disease that a patient lives with the disease, but in which it does not progress.
After a median follow-up of 5.4 years for patients in the SWOG cohort, here is what the researchers found:
- After adjusting for potential confounding factors, patients with vitamin D deficiency (levels less than 20 ng/ml) died at 4.16 times the rate than those with higher levels (p = 0.002).
- Patients with vitamin D deficiency had their disease progress at almost twice the rate (1.97) than those with higher levels, after adjusting for potential confounding factors (p = 0.023).
The researchers found similar results when looking at the LYSA cohort, which had a median follow-up of 6.6 years.
- Patients with vitamin D deficiency (less than 10 ng/ml) had their disease worsen at 1.5 times the rate than those with higher vitamin D levels, after adjusting for potential confounding factors (p = 0.095).
- After adjusting for potential confounding factors, patients with vitamin D deficiency died at 1.92 times the rate than those with higher vitamin D levels. However, this was an insignificant finding (p = 0.192).
The researchers concluded,
“Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival.”
While these results are exciting, the researchers reminded readers of the study’s limitations. Both cohorts had limited number of patients with available blood samples for vitamin D measurement. Therefore, the sample was prone to selection bias. Also, these results do not prove causation due to the observational study design.
Clinical trials are needed to evaluate the effects of vitamin D supplementation on FL outcomes.